TREATT: TRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia

Sponsor

NHS Blood and Transplant (Other)

Overall Status

Completed

CT.gov ID

NCT03136445

Collaborator

National Health and Medical Research Council, Australia (Other), Monash University (Other)

616

Enrollment

Locations

Arms

84.6

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether giving tranexamic acid to patients receiving treatment for blood cancers reduces the risk of bleeding or death, and the need for platelet transfusions. Patients will be randomised to receive tranexamic acid (given intravenously through a drip, or orally) or a placebo.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Neoplasms Hemorrhage Hematopoietic Stem Cell Transplantation	Drug: Tranexamic acid (TXA). Drug: Placebo	Phase 3

Detailed Description

Patients with cancers of the blood often develop low blood cell counts either as a consequence of the disease or the treatment by chemotherapy or stem cell transplantation. Platelet transfusions are commonly given to raise any low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). But recent studies have indicated that many patients continue to experience bleeding, despite the use of platelet transfusions. Tranexamic acid is a type of drug that is called an antifibrinolytic. These drugs act to reduce the breakdown of clots formed in response to bleeding. These drugs have been used widely in both elective and emergency surgery and have been shown to decrease blood loss and the use of red cell transfusions. The purpose of this study is to test whether giving tranexamic acid to patients receiving treatment for blood cancers reduces the risk of bleeding or death, and the need for platelet transfusions. Patients will be randomised to receive tranexamic acid (given intravenously through a drip, or orally) or a placebo. The investigators will measure the rates of bleeding daily using a short structured assessment of bleeding and will record the number of transfusions given to patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

616 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

A Double-blind, Randomised Controlled Trial Evaluating the Safety and Efficacy of Antifibrinolytics (Tranexamic Acid) in Patients With Haematological Malignancies With Severe Thrombocytopenia

Actual Study Start Date :

Jun 1, 2015

Actual Primary Completion Date :

Feb 18, 2022

Actual Study Completion Date :

Jun 18, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Arm Tranexamic acid (TXA). Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.	Drug: Tranexamic acid (TXA). IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid. Other Names: Cyklokapron® trans-4-(aminomethyl)cyclohexanecarboxylic acid Lysteda
Placebo Comparator: Control Arm Placebo (saline) if administration is IV. Placebo tablet matched for appearance to TXA if oral.	Drug: Placebo IV (saline) or oral placebo tablets Other Names: Placebo for tranexamic acid

Arm

Intervention/Treatment

Experimental: Intervention Arm

Tranexamic acid (TXA). Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.

Drug: Tranexamic acid (TXA).

IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid.

Other Names:

Cyklokapron®

trans-4-(aminomethyl)cyclohexanecarboxylic acid

Lysteda

Placebo Comparator: Control Arm

Placebo (saline) if administration is IV. Placebo tablet matched for appearance to TXA if oral.

Drug: Placebo

IV (saline) or oral placebo tablets

Other Names:

Placebo for tranexamic acid

Outcome Measures

Primary Outcome Measures

The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment. [The first 30 days from first dose of trial treatment]
The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment. A time-to-event analysis will be used to determine this proportion to ensure that all patients are included in the primary outcome analysis, not just those who are followed up for the full 30 days. Any patients lost to follow-up will be included in the analysis and censored at the time that they were lost.

Secondary Outcome Measures

Proportion of days with bleeding (WHO grade 2 or above) up to Study Day 30. [The first 30 days from first dose of trial treatment .]
Number of days where WHO grade 2 or above bleeding has been recorded bleeding using WHO bleeding criteria.
Time to first episode of bleeding of WHO grade 2 or greater up to study day 30. [The first 30 days from first dose of trial treatment.]
Bleeding assessed using WHO bleeding criteria.
Highest grade of bleeding a patient experiences up to study day 30. [The first 30 days from first dose of trial treatment.]
Measured using WHO bleeding criteria.
Number of platelet transfusions per patient up to study day 30. [The first 30 days from first dose of trial treatment.]
Measured by number of recorded platelet transfusions per patient.
Number of red cell transfusions per patient up to study day 30. [The first 30 days from first dose of trial treatment.]
Measured by number of recorded red cell transfusions per patient.
Proportion of patients surviving at least 30 days without a platelet transfusion. [The first 30 days from first dose of trial treatment.]
Measured by calculating number of patients surviving at least 30 days without a platelet transfusion.
Proportion of patients surviving at least 30 days without a red cell transfusion. [The first 30 days from first dose of trial treatment.]
Measured by calculating the number of patients surviving at least 30 days without a red cell transfusion.
Number of thrombotic events from first administration of trial treatment up to and including 120 days after the first dose of trial treatment is administered, per day at risk. [Up to and including 120 days from the first administration of investigational medicinal product (IMP).]
Measured by calculating number of clinically diagnosed thrombotic events from Treatment Day 1 i.e the first day that the investigational medicinal product (IMP) is administered, up to and including the next 120 days.
Number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment. [Up to and including 60 days from the first administration of IMP.]
Measured by calculating number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of Treatment Day 1 i.e the first day that the IMP is administered.
All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered. All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered [Up to and including 120 days from the first administration of IMP.]
Measured by calculating number of deaths in first 30 days and 120 days after Treatment Day 1 i.e the first day that the IMP is administered.
Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered. [Up to and including 120 days from the first administration of IMP.]
Measured by calculating number of deaths due to thrombosis during the first 120 days after Treatment Day 1 i.e the first day that the IMP is administered.
Death due to bleeding during the first 30 days after the first dose of trial treatment is administered. [Up to and including 30 days from the first administration of IMP.]
Measured by calculating number of deaths due to bleeding during the first 30 days
Number of serious adverse events (SAE) from first administration of trial treatment until 60 days after the first dose of trial treatment is administered. [Up to and including 60 days from the first administration of IMP.]
Measured by calculating the total number of SAE's reported from first administration of IMP.

Other Outcome Measures

Proportion of days with thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). [Measured during first 30 days from first dose of IMP.]
Measured by number of days that the patient's laboratory results indicate that the patient is thrombocytopenic.
Reasons for platelet and red cell transfusions. [Measured during first 30 days from first dose of IMP.]
Reasons for platelet and red cell transfusions as documented by clinician.
Proportion of days with fever [Measured during first 30 days from first dose of IMP.]
Highest daily temperature ≥ 38.1°C

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients are eligible for this trial if:

Aged ≥18 years of age
Confirmed diagnosis of a haematological malignancy
Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation
Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10⁹/L for ≥ 5 days
Able to comply with treatment and monitoring

Exclusion Criteria:

A patient will not be eligible for this trial if he/she fulfils one or more of the following criteria:

Patients with a past history or current diagnosis of arterial or venous thromboembolic disease including myocardial infarction, peripheral vascular disease and retinal arterial or venous thrombosis.
Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy
Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome)
Patients with known inherited or acquired prothrombotic disorders e.g.
Lupus anticoagulant
Positive antiphospholipids
Patients receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) within 48 hours of enrolment, or with known hypercoagulable state
Patients receiving L-asparaginase as part of their current cycle of treatment
History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS)
Patients with overt disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition)
Patients requiring a platelet transfusion threshold >10x10/⁹L at time of randomisation. (This refers to patients who require their platelet count to be maintained at a certain specified level on an ongoing basis, and excludes a transient rise in the threshold due to sepsis.)
Patients with a known inherited or acquired bleeding disorder e.g.
Acquired storage pool deficiency
Paraproteinaemia with platelet inhibition
Patients receiving anticoagulant therapy or anti-platelet therapy
Patients with visible haematuria at time of randomisation
Patients with anuria (defined as urine output < 10 mls/hr over 24 hours).
Patients with severe renal impairment (eGFR ≤30 ml/min/1.73m²)
Patients with a previous history of epilepsy, convulsions, fits or seizures
Patients who are pregnant or breast-feeding
Allergic to tranexamic acid.
Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.
Patients previously randomised into this trial at any stage of their treatment.

Contacts and Locations

Locations

	Site	City	Country
1	Royal Adelaide Hospital	Adelaide	Australia
2	Royal Brisbane	Brisbane	Australia
3	Canberra Hospital	Canberra	Australia
4	Andrew Love Cancer Centre	Geelong	Australia
5	Alfred Hospital	Melbourne	Australia
6	Monash Health	Melbourne	Australia
7	St Vincent's Hospital	Melbourne	Australia
8	Victorian Comprehensive Cancer Centre	Melbourne	Australia
9	Royal North Shore Hospital	St Leonards	Australia
10	St Vincent's Hospital	Sydney	Australia
11	Westmead Hospital	Westmead	Australia
12	Royal United Hospital	Bath	United Kingdom
13	Belfast City Hospital	Belfast	United Kingdom
14	Heartlands Hospital	Birmingham	United Kingdom
15	Queen Elizabeth Hospital	Birmingham	United Kingdom
16	Bristol Haematology and Oncology Centre	Bristol	United Kingdom
17	University Hospital Coventry	Coventry	United Kingdom
18	Royal Devon and Exeter Hospital	Exeter	United Kingdom
19	Beatson West of Scotland Cancer Centre	Glasgow	United Kingdom
20	St James's Hospital	Leeds	United Kingdom
21	Lincoln County Hospital	Lincoln	United Kingdom
22	King's College Hospital	London	United Kingdom
23	University College London Hospitals	London	United Kingdom
24	Freeman Hospital	Newcastle	United Kingdom
25	Churchill Hospital	Oxford	United Kingdom
26	Derriford Hospital	Plymouth	United Kingdom
27	Salisbury District Hospital	Salisbury	United Kingdom
28	Royal Hallamshire Hospital	Sheffield	United Kingdom

Sponsors and Collaborators

NHS Blood and Transplant
National Health and Medical Research Council, Australia
Monash University

Investigators

Principal Investigator: Lise J Estcourt, MBBChir MSc DPhil MRCP FRCPath, NHS Blood and Transplant
Principal Investigator: Zoe K McQuilten, MBBS PhD, Monash University
Principal Investigator: Simon J Stanworth, DPhil FRCP FRCPath, NHS Blood and Transplant
Principal Investigator: Erica M Wood, MB BS, FRACP, FRCPA, Monash University